P-Chloroaniline

Reaction of p-chloroaniline with dicyanamide affords the biguan-ide, 182. This is condensed immediately with acetone to form the aminal cycloguanil (183). The compound is usually used as a salt with pamoic acid (184). 

A preparation of authentic 3a was then undertaken. Reaction of p-chloroaniline with benzoyl chloride in the presence of zinc... 

Many other systems have been disclosed (85a). Pressure has a marked effect on the course of this reduction, especially when excess morpholine is used. At low pressure (< 50 psi) complete displacement of halogen by morpholine occurs to give p-(N-morpholino)nitrobenzene above 200 psi, the product is p-chloroaniline (55). 

Trimethyl-6(47/)-quinoxalinimine (304) with diazotized p-chloroaniline gave 3-p-chlorophenylazomethyl-2,4-dimethyl-6(47/)-quinoxalinimine (305)... 

The wide latitude of structural variation consistent with bioactivity in this series is illustrated by the observation that antiinflammatory activity is maintained even when the second aromatic group is attached directly to the pyrrole nitrogen rather than to the heterocyclic ring via a carbonyl group as in the previous case. Condensation of p-chloroaniline with hexane-2,5-dione (or its dimethoxy-tetrahydrofuran equivalent) affords pyrrole 7. The acetic acid side chain is then elaborated as above. Thus, Mannich reaction leads to the dimethylaminomethyl derivative 8, which is in turn methylated (9) the quaternary nitrogen replaced by cyanide to afford 10. Hydrolysis of the nitrile then gives clopirac (11). 

Tricyclic antihistamines as a rule carry aliphatic nitrogen as a substituent on a side chain attached to the central ring the side chain nitrogen may be part of a heteroaromatic ring. Conjugate addition of p-chloroaniline (49) to the substituted vinylpyridine 50 gives the alkylated aniline 51. Treatment of that intermediate with nitrous acid leads to N-nitroso intermediate 52 which is then reduced to the hydrazine (53). Reaction of 53 with N-methyl-4-piperidone... 

The pyrazolotriazinecarboxylate 708 underwent cyclization with urea or thiourea to give (84PHA432) pyrazolopyrimidinotriazines 711, and with o-phenylenediamine, p-chloroaniline, or o-aminophenol to give quinolino-pyrazolotriazines 710. The reaction of the pyrazolo[5,l-c][I,2,4]triazine 709 with hydrazine hydrate gave 712, and its reaction with phenyl isothiocyanate gave 713 (83G219). 

Wahner, A., Zetzsch, C. (1983) Rate constants for the addition of hydroxyl radicals to aromatics (benzene, p-chloroaniline, and o-, m- and p-dichlorobenzene) and the unimolecular decay of the adduct. Kinetics into a quasi-equilibrium. J. Phys. Chem. 87, 4945 -951. 

Goodman, D.G., J.M.Ward, and W.D.Reichardt. 1984. Splenic fibrosis and sarcomas in F344 rats fed diets containing aniline hydrochloride, p-chloroaniline, azobenzene, o-toluidine hydrochloride, 4,4 -sulfonyldianiline, or D C red no. 9. J. Natl. Cancer Inst. 73 265-273. 

Similar chemistry was used to synthesize pyridyl(methyl)phthalazines, 193, inhibitors of the VEGF receptor tyrosine kinase. The active inhibitors 193 were formed by condensation of 192 with hydrazine, followed by POCI3 chlorination. <00JMC2310>. Furthermore, a simple substitution reaction with p-chloroaniline gave anilinophthalazine 194. 

The above-mentioned Pigment Green 10 is the 1 2 nickel complex of the azo pigment obtained from p-chloroaniline and 2,4-dihydroxy-quinoline (33) ... 

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